Background: Apnea of prematurity is almost universal in infants who are born before 34 weeks gestation. Previous randomised trials and systematic reviews have found methylxanthines to be effective in preventing apnea of prematurity. However, recent concerns about potential long term side effects of methylxanthines on the neurodevelopment of low birth weight infants have led to an increased interest in alternate methods of treating apnea of prematurity. Nasal continuous positive airway pressure (NCPAP) is a useful method of respiratory support which reduces the incidence of obstructive or mixed apnea. However, apneic infants managed with NCPAP, with or without methylxanthines, sometimes require endotracheal intubation with its attendant morbidity and cost. Nasal intermittent positive pressure ventilation (NIPPV) is a simple, effective mode of respiratory support for older children and adults. It has been used to treat apnea in preterm infants but case reports of gastrointestinal perforations have limited its widespread use.
Objectives: In preterm infants with recurrent apnea, does treatment with NIPPV lead to a greater reduction in apnea and need for intubation and mechanical ventilation, as compared with treatment with NCPAP? Does NIPPV increase the incidence of gastrointestinal complications, i.e. gastric distension leading to cessation of feeds, or perforation?
Search strategy: MEDLINE was searched (1966-Oct week 2, 2001). Other sources included the Cochrane Controlled Trials Register (Cochrane Library, Disk Issue 3, 2001) and CINAHL (1982-Sept week 4, 2001). Also used were expert informants, previous reviews including cross-references, and conference and symposia proceedings.
Selection criteria: All randomised and quasi-randomised trials were included. Participants included unventilated preterm infants experiencing apnea of prematurity. Interventions compared were intermittent positive pressure ventilation administered via the nasal route, either by short nasal prongs or nasopharyngeal tube, and nasal CPAP delivered by the same methods. Types of outcome measures: - failure of therapy as defined by apnea that is frequent or severe requiring additional ventilatory support - rates of endotracheal intubation - rates of apnea and bradycardia expressed as events per hour - gastrointestinal complications i.e. abdominal distension requiring cessation of feeds, or GI perforation
Data collection and analysis: Data were extracted independently by the three reviewers. The trials were analysed using relative risk (RR), risk difference (RD) and number needed to treat (NNT) for dichotomous data; means and weighted mean difference (WMD) were used for continuous data.
Main results: Two trials, enrolling 54 infants in total, fulfilled the inclusion criteria. Both reported only the short term results (4 to 6 hours) of the interventions. Only one infant (randomised to NCPAP) required intubation during this period. Ryan (1989), in a cross over study of 20 infants, showed no significant difference in rates of apnea (events/hr) between the 2 interventions [WMD -0.10 (-0.53,0.33)]. Lin (1998) randomised 34 infants and demonstrated a greater reduction in frequency of apneas (events/hr) with NIPPV compared to NCPAP [WMD -1.19 (-2.31,-0.07)]. Meta-analysis of both trials showed no difference in pCO2 (mmHg) at the end of the 4-6 hour study period [WMD 0.95 (-3.05,4.94)]. No data were reported on gastrointestinal complications.
Implications for practice: NIPPV may be a useful method of augmenting the beneficial effects of NCPAP in preterm infants with apnea that is frequent or severe. Its use appears to reduce the frequency of apneas more effectively than NCPAP. Additional safety and efficacy data are required before recommending NIPPV as standard therapy for apnea.
Implications for research: Future trials with sufficient power should assess the efficacy (reduction in failure of therapy) and safety (GI complications) of NIPPV. Outcomes should be assessed throughout the entire period during which the infant requires assisted ventilation. The recent ability to synchronise NIPPV with an infant's spontaneous respirations is a promising development requiring further assessment.